As many enzymes and cell surface receptors possess handedness, the enantiomers of a racemic pair of compounds may be absorbed, activated, and/or degraded in different manners. In some instances, two racemates of a given drug may have different or even opposite pharmacological activities. This aspect in conjunction with other factors within the pharmaceutical industry have stimulated the need for enantiomerically pure intermediates and bulk optically active compounds. Quick access to reasonable amounts of chiral materials to assess their pharmaceutical activity is highly desirable to many pharmaceutical companies. Among the asymmetric technologies developed to analyze and separate optically active compounds, the direct separation of enantiomers by HPLC on chiral stationary phases has been a subject of intense investigation. As a result, a wide variety of chiral stationary phases have been developed. Although a thorough evaluation of all the current chiral columns is impossible, the commonly used chiral columns do seem to have their limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This proposal is intended for the rapid development of more efficient stationary phases for chiral chromatography. Specifically, combinatorial library approaches are proposed for the development of chiral stationary phases. These methods will be applied to develop efficient chiral stationary phases for separating racemates of several compounds of pharmaceutical importance. The chemistry associated with the characterization of chiral stationary phases on silica gel will also be studied.